Selecting Appropriate Adjuvant Therapy for Patients with EGFR-Mutant NSCLC

Dr. Zofia Piotrowska: So maybe with that, let's talk a little bit about how we select systemic therapy for these patients. I think first maybe let's talk- Nick, you're seeing this patient after surgery. So, we're following the patient journey. The patient's had a resection and they're coming to you now. And so, how do you talk about- with them about adjuvant therapy? And I think this is probably a point too to talk about the role of both chemotherapy and the TKI, which we've already started to touch on.

Dr. Nicholas Rohs: Absolutely. So, as you- as you alluded to, this is a journey the patient is going on and they start with an interventionalist getting a biopsy. And I love the fact that Gus was talking about setting the stage. Because I think that's so important. Setting appropriate expectations for the patient. Because as they go throughout their journey, you're going to have new pieces of information for them to digest. And then making sure that we get quick testing done is really important. But we all live in a very lucky world where we have often reflexive in-house testing and really fancy panels we're running at our large academic institutions. But that's not often the case for a lot of people in the community and throughout the world. So, this is really a challenge, and we have to continue to advocate for getting these biomarker tests quickly and efficiently done for our patients because sometimes they show up at my door without this information. And that's the most challenging situation for me. How do I inform you if I don't have this information? But in a perfect world, if I do, then I can have a really good, informed discussion with my patient. You've had your treatment for your- with surgery, this tumor is removed, and I hope we are sitting in a cancer-free room right now where you are cured of cancer. But there is a real chance that the disease is going to come back, and we have a couple of options in front of us. And if I have that biomarker testing, I can think about immunotherapy, I can think about chemotherapy, and I can think about targeted therapy with Osimertinib. And that allows me to pick the right pathway for the patient. So, since we're focusing on eGFR, I'll talk about that some more. We're all excited about this data. This is amazing. This is great. And I think a lot of us are going to adopt Osimertinib adjuvant for these patients. But we can't forget chemotherapy. Chemotherapy is so critical for these patients because it is now these- one of the two things that are improving overall survival, but it does improve overall survival. So, we don't want to just say, oh, let's just go with the pill and forget about the chemotherapy. So, you have to think about the patient in front of you. They've been through surgery, they're still recovering, so nobody feels like rushing to chemotherapy. But we do know that that's an important thing for our patients to do. So, we have to select the right patient and make sure they have the right organ function, the hematologic function, and that's in line with their goals of care. So, you have that risk-benefit. Because on average, we're adding about a 5% reduction of recurrence risk with chemotherapy. But that's a real number and we have that discussion. And then I have a secondary discussion, or I guess kind of a co-mingled discussion these days of- And then if you have this eGFR mutation, you have Osimertinib available to you. And as we talked about before, depending on the stage, the benefit can go up in grade. But that for most patients, 1B through 3A, this is going to be benefiting you, letting you live longer and hopefully better. And I think that's the really important discussion we have. And then, of course, we can think about some other novel therapies like postoperative radiation therapy, but those are falling out of favor pretty quickly. Especially based off of the Lung ART trial that showed that it did improve local control, but not necessarily survival, given the cardiotoxic effects of the radiation. So, it's becoming a really hard conversation, but I always remember at the end of that conversation is a patient who has a life to live, and I want to make sure that we're making the right decision for that patient in front of me.

Dr. Zofia Piotrowska: Absolutely. I think it's really important to drill down on this question about chemotherapy a little bit more. This was a big topic of discussion around ADUARA, and I think continues to be. So, I want to kind of pull our other medical oncologist. How do you view the role of chemotherapy? Is it different at all in the light of ADUARA or do you view those as separate decisions?

Dr. Lyudmila Bazhenova: I think it's a separate decision. I think ADUARA did not prove to us that we can stop giving adjuvant chemotherapy. That was not the question that was designed to be answered by ADUARA. As Nick said, this is a proven way to increase the cure rate of early-stage lung cancer. Yes, the number is small, but there is a number. And I think until you tell me that you run a randomized study where you compare eGFR- patients with eGFR mutations who are randomized to chemotherapy followed by Osimertinib versus Osimertinib, I will continue to offer chemotherapy to my patients.

Dr. Zofia Piotrowska: Ashish, what do you think about it?

Dr. Ashish Saxena: I think I totally agree. I think the study didn't answer that question. It wasn't meant to answer the question of whether you need chemotherapy or not. The patients that got or didn't get chemotherapy were based on their own preferences and decision. It wasn't a randomization. It wasn't anything controlled. So, I don't think we can say that chemotherapy is not needed. And I think we would- I would continue to use it the way I was using it even before ADUARA. It's adjuvant, you have stage two, stage three lung cancer. I know, as Nick and Luda said that there's data that the chemotherapy is going to improve your overall survival.

Dr. Nicholas Rohs: And I think if we look at the appendix that actually the chemotherapy- patients who receive chemotherapy, there is a trend towards better survival. So, we can't forget about the importance of this.

Dr. Zofia Piotrowska: I totally agree, and I hope that maybe in the future we will have that study, Luda. I think it would be such an incredibly important study. In the past, we've had kind of either-or studies largely done with older first and second-generation eGFR inhibitors randomized against chemotherapy done in Japan and China. And we didn't see an improvement in survival there. But I think it's a different question now in the setting of Osimertinib. And so, perhaps we'll have more information. But for now, I agree. I think these are two separate conversations that you need to have with these patients. And these decisions have to be made independently of one another.

Dr. Jay Moon Lee: If I could just add to that, as a surgeon, I always get- I am- I'm the immediate second opinion. As soon as the patient sees the medical oncologist, should I get the chemo? And what I tell my patients when they ask me this question with the issue of chemo or not in ADUARA, if you look- Yes, it is true that 40% of the patients didn't get chemo in ADUARA, but when you look at it by stage, stage 1B, 85% didn't get it. When you look at stage two, 30% didn't get it. And when you look at stage three, 19% didn't get it. Medical oncologists feel that you follow the indications for chemo separate from the issue of OSI. And the higher the stage, the patients are more likely to receive it. So, I think it's more stage dependent rather than a yes-no binary issue of yes or no chemo. I think it's still dependent on how you would deliver chemo or recommend it, which is stage directed.

Dr. Nicholas Rohs: Absolutely. I don't think this should change the discussion we used to have about chemotherapy, about the stratification of risk benefits. So that's a really important point.

Dr. Zofia Piotrowska: Absolutely.